title: Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells.
abstract: Interactions between glioma cells and their local environment are critical determinants of brain tumor growth, infiltration and neovascularisation. Communication with host cells and stroma via microvesicles represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. Here we have taken an unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells. We find that glioma microvesicles are predominantly of exosomal origin and contain complex populations of coding and noncoding RNAs in proportions that are distinct from those in the cells from which they are derived. Microvesicles show a relative depletion in microRNA compared with their cells of origin, and are enriched in unusual or novel noncoding RNAs, most of which have no known function. Short-term exposure of brain microvascular endothelial cells to glioma microvesicles results in many gene expression changes in the endothelial cells, most of which cannot be explained by direct delivery of transcripts. Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized.
authors.affiliation: Victor Chang Cardiac Research Institute; Sydney, Australia.
authors.forename: Cheryl C Y
authors.initials: CC
authors.lastname: Li
authors.forename: Sally A
authors.initials: SA
authors.lastname: Eaton
authors.forename: Paul E
authors.initials: PE
authors.lastname: Young
authors.forename: Maggie
authors.initials: M
authors.lastname: Lee
authors.forename: Rupert
authors.initials: R
authors.lastname: Shuttleworth
authors.forename: David T
authors.initials: DT
authors.lastname: Humphreys
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
authors.forename: Valery
authors.initials: V
authors.lastname: Combes
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
authors.forename: Joyce
authors.initials: J
authors.lastname: Gong
authors.forename: Susan
authors.initials: S
authors.lastname: Brammah
authors.forename: Michael E
authors.initials: ME
authors.lastname: Buckland
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Suter
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D055806:Microvessels / Q000166:cytology; D009389:Neovascularization, Pathologic; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D022661:RNA, Untranslated
keywords: exosome; gene expression; glioblastoma; microparticle; small noncoding RNA; vault RNA